In general, the delivery of therapeutic substances to the surface of the eye has inherent difficulties because the washing action of the tear film removes much of the therapeutic substance. Typically, 90% or more of an ophthalmic drug in the form of an eye drop does not penetrate or adhere to the eye and is removed by tears through the lachrymal ducts.
Anionic therapeutic agents may lack affinity for the surface of an eye due to the anionic nature of the surface of the eye. Thus, the therapeutic effect provided by such agents may be short lived due to the rate at which the agent is flushed away from the eye. Attempts to solve this problem have resulted in the development of delivery systems for therapeutic agents. For example, U.S. Pat. No. 5,358,706 to Marlin et al. discloses a delivery system comprising a cationic polysaccharide in order to bind anionic therapeutic agents to the surface of the eye. Exemplary anionic therapeutic agents are glycosaminoglycans such as hyaluronic acid for the treatment of dry eye, as disclosed by Marlin et al. Synthetic anionic polymers have also been shown to be effective for the treatment of dry eye, for example, the carboxy vinyl polymers disclosed in U.S. Pat. No. 5,209,927 to Gressel et al. Combinations of cationic polymers (as delivery vehicles) with anionic therapeutic agents have also been used in the treatment of keratinous tissues such hair, skin and nails. See, for example, U.S. Pat. Nos. 4,913,743 and 4,767,463 to Brode et al.
U.S. Pat. No. 5,192,535 to Davis et al. discloses a topical ophthalmic medicament delivery method and system that employs carboxy vinyl polymers having certain physical properties that provide for the controlled, sustained release of medicaments after administration in drop form. The delivery system is designed to be administrable at a viscosity suitable for reliable drop dosages, but to substantially increase in viscosity after administration.
It is also possible to provide for the delivery of therapeutic agents with the aid of contact lenses as a delivery device, especially if the person being treated wears contact lenses anyway. Although not related to the delivery of a therapeutic agent, a variety of cationic compounds have been used to temporarily modify the surface properties of contact lens. For example, cationic polymers have been used in aqueous compositions for lubricating and cushioning rigid gas permeable (RGP) lenses. Since RGP lenses typically have an anionically charged surface, cationic polymers tend to associate with the lens surface and can remain associated for an extended period of time. Examples of such cationic polymer are the cationic cellulosic polymers described in U.S. Pat. Nos. 4,168,112 and 5,401,327 to Ellis et al. As indicated above, U.S. Pat. No. 5,358,706 discloses similar cationic polymers as delivery vehicles for therapeutic agents.
Other cationic compounds have also been used to modify the surface properties of contact lenses. For example, quaternary nitrogen-containing ethoxylated glycosides are described in U.S. Pat. No. 5,405,878 to Ellis et al for use in contact-lens care solutions. These compounds each comprise a cationic hydrophobic moiety attached to an ammonium ion and a hydrophilic moiety consisting of a polyethoxylated glycoside derivative, preferably an alkylated glycoside. It is believed that the cationic moiety associates with the negatively charged surface of a lens, while the hydrophilic moiety extends from the lens surface to maintain moisture near the lens surface.
In administering therapeutic agents to the eye, a variety of factors, including consistency and accuracy of dosage, type and time of vision interference, ease of administration, and timing of delivery can be important. Prior ophthalmic delivery vehicles have suffered drawbacks in one or more respects and, in any case, improvement in performance is always desirable. New topical ophthalmic delivery systems for controlled, sustained release of therapeutic agents are, therefore, continually being developed. It is especially challenging to find an ophthalmic delivery vehicle that is safe and effective for human use and that does not have undesirable aide effects or cause undesirable interactions between components in a solution, particularly when limited to use in buffered solutions having osmolality values most common for in-eye solutions (typically from 270 to 330 mOsmols/kg).